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Warnings & Precautions
PRECAUTIONS
Drug Interaction with Erythromycin and Ketoconazole Fexofenadine hydrochloride has been shown to exhibit minimal (ca. 5%) metabolism. However, co-administration of fexofenadine hydrochloride with ketoconazole and erythromycin led to increased plasma levels of fexofenadine hydrochloride. Fexofenadine hydrochloride had no effect on the pharmacokinetics of erythromycin and ketoconazole. In two separate studies, fexofenadine hydrochloride 120 mg twice daily (two times the recommended twice daily dose) was co-administered with erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady state conditions to normal, healthy volunteers (n=24, each study). No differences in adverse events or QTc interval were observed when patients were administered fexofenadine hydrochloride alone or in combination with erythromycin or ketoconazole. The findings of these studies are summarized in the following table: Text Continues Below
Effects on steady-state fexofenadine hydrochloride pharmacokinetics after 7 days of co-administration with fexofenadine hydrochloride 120 mg every 12 hours (two times the recommended twice daily dose) in normal volunteers (n=24)Concomitant DrugCmaxSS (Peak plasma concentration)AUCss(0-12h) (Extent of systemic exposure)Erythromycin (500 mg every 8 hrs)+82%+109%Ketoconazole (400 mg once daily)+135%+164%The changes in plasma levels were within the range of plasma levels achieved in adequate and well-controlled clinical trials. The mechanism of these interactions has been evaluated in in vitro, in situ, and in vivo animal models. These studies indicate that ketoconazole or erythromycin co-administration enhances fexofenadine gastrointestinal absorption. In vivo animal studies also suggest that in addition to increasing absorption, ketoconazole decreases fexofenadine hydrochloride gastrointestinal secretion, while erythromycin may also decrease biliary excretion. Page: 1 | 2 | 3 | 4 | Next >>
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